Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China; Department of Emergency, The First Hospital of Handan, Handan, Hebei 056002, PR China.
Department of Neurology, The First Hospital of Handan, Handan, Hebei 056002, PR China.
Biochem Biophys Res Commun. 2014 Jun 13;448(4):414-7. doi: 10.1016/j.bbrc.2014.04.130. Epub 2014 May 4.
Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.
认知障碍是癫痫最常见和最严重的共病之一，极大地降低了生活质量。然而，目前治疗癫痫的干预措施也可能会引起认知方面的不良反应。因此，我们迫切需要针对癫痫发作和认知障碍的新型药物。氧化应激被认为在癫痫发生和认知缺陷中起重要作用，抗氧化剂具有潜在的抗癫痫作用。二甲双胍是最常用的处方降糖口服药物，具有抗氧化特性。本研究旨在评估二甲双胍对戊四氮（PTZ）诱导的点燃动物的癫痫发作、认知障碍和脑氧化应激标志物的改善作用。雄性 C57BL/6 小鼠每隔一天腹腔注射亚惊厥剂量的 PTZ（37mg/kg），共 14 次。二甲双胍以 200mg/kg 的剂量腹腔注射，并与隔日 PTZ 一起使用。我们发现二甲双胍抑制了点燃的进展，改善了认知障碍，并降低了大脑的氧化应激。因此，本研究得出结论，二甲双胍可能是一种治疗癫痫的潜在药物，也是一种预防癫痫发作引起的认知障碍的保护药物。
